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Autoradiographic mapping of dopamine‐D 2 /D 3 receptor stimulated [ 35 S]GTPγS binding in the human brain
Author(s) -
Sóvágó Judit,
Makkai Boglárka,
Gulyás Balázs,
Hall Håkan
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04192.x
Subject(s) - raclopride , dopamine , quinpirole , medicine , gtp' , endocrinology , dopamine receptor , agonist , chemistry , dopamine receptor d1 , substantia nigra , dopamine receptor d2 , stimulation , receptor , biology , dopaminergic , biochemistry , enzyme
Agonist stimulated [ 35 S]guanosine 5′‐γ‐thiotriphosphate ([ 35 S]GTPγS) binding autoradiography was established for the examination of dopamine‐D 2 /D 3 receptors in human brain sections. The distribution of G proteins activated by dopamine‐D 2 /D 3 receptors was studied in whole hemisphere cryosections. Dopamine stimulated [ 35 S]GTPγS binding in brain regions with high densities of dopamine D 2 ‐like receptors, i.e. putamen (23 ± 2%, mean ± SEM,% stimulation over basal binding), caudate (20 ± 0%) and substantia nigra (22 ± 2%), but also in regions with lower receptor densities such as amygdala (17 ± 8%), hippocampus (16 ± 6%), anterior cingulate (13 ± 3%), and thalamus (12 ± 2%). Dopamine stimulated [ 35 S]GTPγS binding to significantly higher levels in the dorsal than in the ventral part of the striatum. Dopamine caused low or very low stimulation in all cortical areas. Raclopride, a selective D 2 /D 3 receptor antagonist, potently inhibited dopamine stimulated [ 35 S]GTPγS binding, whereas R(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (SCH23390), a selective D 1 antagonist, did not block the [ 35 S]GTPγS binding response stimulated by dopamine. Hence, the stimulatory effect of dopamine was primarily mediated by D 2 /D 3 receptors. Quinpirole stimulated [ 35 S]GTPγS binding in the same regions as dopamine. The maximal level of stimulation induced by dopamine and quinpirole was not significantly different. The present study demonstrates that agonist stimulated [ 35 S]GTPγS binding autoradiography could be a suitable technique for the examination of dopamine‐D 2 /D 3 receptors in the human brain. This functional assay could provide useful new information about dopamine receptor/G protein coupling in the postmortem human brain, and reveal possible disease related alterations of the interaction between D 2 /D 3 receptors and G proteins.